Cytokines are proteins secreted by a cell of the immune system and transduce a signal to a specific cell. Cytokines have various kinds, and many of them are especially associated with immunity and inflammation and also associated with cell growth, differentiation, cell death, wound healing and the like (Curr Opin Cell Biol. 1991 Apr.; 3(2):171-5.).
The janus kinase (JAK) family plays a role in cytokine-dependent regulation of the function of cells associated with growth and immune response. Tyk2 is one of the four kinds of janus kinases (JAK1 (janus kinase 1), JAK2 (janus kinase 2), JAK3 (janus kinase 3) and Tyk2 (tyrosine kinase 2)), and it is known to be involved in signal transduction of cytokines such as IFN (interferon)-α, IFN-β, IL (interleukin)-6, IL-10 family (IL-10, IL-19, IL-20, IL-22, IL-28, IL-29), IL-12, IL-23 and the like (Nature Immunology 10, 356-360 (2009), New York Academy of Science 1246, 34-40 (2011)). These cytokines play an important role in immune response when exist in an appropriate amount. However, excessive production of them is involved in many autoimmune diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus and the like (Journal of Allergy and Clinical Immunology 127, 3,701-721.e70 (2011), Cytokine & Growth Factor Reviews 19, 41-52 (2008), Invest Ophthalmol Vis Sci. 2008 July; 49(7):3058-3064, Ann Rheum Dis. 2010 July; 69(7):1325-1328). For example, Ustekinumab, which is an anti-IL-12/23 monoclonal antibody, has been approved as a therapeutic drug for moderate to severe psoriasis patient in Europe, and furthermore, clinical trials for various diseases in which the IL-12/23 signaling pathway is suggested to be involved are performed. From the foregoing, a Tyk2 inhibitor is a therapeutic drug for various autoimmune diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus and the like (Front Biosci. 2011 Jun. 1; 17:3214-32).
Examples of the compound having a structure similar to the compound described in the present specification include the following compounds.
(1) A compound represented by the following formula:
wherein(I) X is CH or N;                R1 is halogen;        R2 is H, halogen, cyano, an optionally substituted nitrogen-containing non-aromatic heterocyclic group or the like;        R3 is H or alkyl;        R4 is H or alkyl; and        R5 is H or alkyl; or(II) X is —CRA;        RA is a group represented by the following formula:        
                                    wherein            * means a binding position; and            RB is an optionally substituted amino or the like;                        R1 is halogen;        R2 is H;        R3 is H or hydroxy;        R4 is H or alkyl; and        R5 is H or alkyl,which is a JAK2 inhibitor, and is useful for the treatment of inflammatory disease and the like (Patent Document 1).(2) A compound represented by the following formula:        
whereinR1 is optionally substituted C1-4 alkyl or the like;R2 is optionally substituted phenyl or the like; andR3 is an optionally substituted aromatic heterocyclic group or the like,which is a HIV transcription inhibitor, and is useful for the treatment of HIV and the like (Patent Document 2).(3) A compound represented by the following formula:
whereinX is an nitrogen-containing heterocycle or the like;Y is —NR6— or the like;R1 and R2 are independently hydrogen, an optionally substituted alkyl group or the like;R5 is an optionally substituted alkyl group, an optionally fused aryl group or the like; andR6 is an optionally substituted alkyl group or the like, which is an agent for the prophylaxis or treatment of viral infectious (Patent Documents 3 and 6).(4) A compound represented by the following formula:
whereinR1 is a hydrogen atom or an alkyl group;R2 is an optionally substituted aryl group, an optionally substituted heteroaryl group or the like;Z is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group or the like;J is a hydrogen atom, an optionally substituted alkyl group or the like; andL is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group or the like,which is a PDE inhibitor, and is useful as an agent for the prophylaxis or treatment of inflammatory disease (rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and the like) and the like (Patent Document 4).(5) A compound represented by the following formula:
whereinR1 is
R2, R3, R4, Ra and Rb are independently a hydrogen atom, an optionally substituted alkyl group or the like;R5 and R6 are independently a nitrogen-containing heterocycle or the like;X is O, S, N(Rk) or the like;Y is O, S, (CHRg)m, N(Rk) or the like;Q, U and V are independently N or CRg or the like;Rk is a hydrogen atom, an optionally substituted alkyl group or the like;Rq is a hydrogen atom, an optionally substituted alkyl group or the like; andM is 0, 1, 2, 3 or 4,which is a c-Rel inhibitor, and is useful as an agent for the prophylaxis or treatment of inflammatory disease (rheumatoid arthritis, psoriatic arthropathy, systemic lupus erythematosus and the like) and the like (Patent Documents 5 and 7).